Specific Infections Research Articles

HIV Tissue Reservoirs: Current Advances in Research.

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), has become a heavy burden of disease and an important public health problem in the world. Although current antiretroviral therapy (ART) is effective at suppressing the virus in the blood, HIV still remains in two different types of reservoirs-the latently infected cells (represented by CD4+ T cells) and the tissues containing those cells, which may block access to ART, HIV-neutralizing antibodies and latency-reversing agents. The latter is the focus of our review, as blood viral load drops below detectable levels after ART, a deeper and more systematic understanding of the HIV tissue reservoirs is imperative. In this review, we take the lymphoid system (including lymph nodes, gut-associated lymphoid tissue, spleen and bone marrow), nervous system, respiratory system, reproductive system (divided into male and female), urinary system as the order, focusing on the particularity and importance of each tissue in HIV infection, the infection target cell types of each tissue, the specific infection situation of each tissue quantified by HIV DNA or HIV RNA and the evidence of compartmentalization and pharmacokinetics. In summary, we found that the present state of HIV in different tissues has both similarities and differences. In the future, the therapeutic principle we need to follow is to respect the discrepancy on the basis of grasping the commonality. The measures taken to completely eliminate the virus in the whole body cannot be generalized. It is necessary to formulate personalized treatment strategies according to the different characteristics of the HIV in the various tissues, so as to realize the prospect of curing AIDS as soon as possible.

Estimating antibiotic coverage from linked microbiological and clinical data from the Swiss Paediatric Sepsis Study to support empiric antibiotic regimen selection.

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011-2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important.

Oncolytic adenovirus-loaded magnetic-driven Janus tumor cell robots for active and targeted virotherapy of homologous carcinoma

This work presents oncolytic adenovirus (OA)-loaded Janus tumor cell-based microrobots fabricated by asymmetrically coating OA-infected tumor cells with Fe3O4 nanoparticles (NPs), capable of homologous adhesion, active virotherapy, and magnetic navigation in complex topography. The cellular resources allow the infected OA to replicate inside the host cell, further inducing cytolysis to release the viral progeny for persistent and specific tumor infection and killing. The resulting cell robots preserve the intrinsic feature of tumor cells with cognate adhesion to homologous cancerous cells. The effective magnetic propulsion coupling with homologous binding of Janus cell robots greatly enhance their binding and penetration to three-dimensional (3D) homologous tumor cell spheroid with improved cell-killing efficacy. Moreover, cell robots can be navigated across the confined space and migrate from the bladder to the renal area through the ureter in the excised rabbit urinary system upon magnetic manipulation. Imparting tumor cells with magnetic propulsion force and virus cargos generates a motile therapeutic platform with the capability of tumor-specific killing and binding, and robust and steerable motion, holding great potential to cross the inherent barriers inside living body and achieve efficient drug delivery toward hard-to-reach sites upon minimized invasion and toxicity to healthy tissues.

Pediatric Sepsis: a Summary of Current Definitions and Management Recommendations.

Pediatric sepsis remains an important cause of morbidity and mortality in children. This review will summarize the main aspects of the definition, the current evidence base for interventions discuss some controversial themes and point towards possible areas of improvement. Controversy remains regarding the accurate definition, resuscitation fluid volume and type, choice of vasoactive/inotropic agents, and antibiotic depending upon specific infection risks. Many adjunctive therapies have been suggested with theoretical benefits, although definitive recommendations are not yet supported by data. We describe best practice recommendations based on international guidelines, a review of primary literature, and a discussion of ongoing clinical trials and the nuances of therapeutic choices. Early diagnosis and timely intervention with antibiotics, fluid resuscitation, and vasoactive medications are the most important interventions in sepsis. The implementation of protocols, resource-adjusted sepsis bundles, and advanced technologies will have an impact on reducing sepsis mortality.

Assessment of the knowledge, attitudes and perceived quality of education about antimicrobial use and resistance of medical students in Zambia, Southern Africa.

Antimicrobial resistance (AMR) is a major global health threat, particularity in lower-middle-income countries (LMICs) where antibiotics are readily available, leading to antibiotic misuse. Educational interventions are lacking in Zambia. Our study assessed antimicrobial use and resistance knowledge, attitude and perceived quality of education relating to AMR in Zambian medical schools. A cross-sectional anonymous survey of students at six accredited medical schools in Zambia using a self-administered questionnaire was administered, using Qualtrics. Chi-squared, Fisher exact test, Pearson correlation test and Student's t-tests were performed for descriptive analyses. Multivariable logistic regression was used to examine associations between knowledge and antibiotic use, beliefs and behaviours. Analysis was performed in SAS version 9.4. One hundred and eighty responses from six medical schools were included in the final analysis. Fifty-six percent of students rated their overall education on antibiotic use as useful or very useful. Ninety-one percent thought that antibiotics are overused, and 88% thought resistance was a problem in Zambia. Only 47% felt adequately trained on antibiotic prescribing, and 43% felt confident in choosing the correct antibiotic for specific infections. Only 2% felt prepared interpreting antibiograms, 3% were trained to de-escalate to narrow-spectrum antibiotics, 6% knew how to transition from IV antibiotics to oral antibiotics, 12% knew of dosing and duration, and 14% understood the spectrum of activity of antibiotics. Forty-seven percent of respondents think hand hygiene is unimportant. Medical students in Zambia expressed a good level of knowledge, but low levels of training and confidence regarding antimicrobial prescribing practices and resistance. Our study highlights training gaps and possible areas of intervention in the medical school curriculum.

All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study

Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. The Bill & Melinda Gates Foundation.

A Single Nonsynonymous Substitution in the RNA-Dependent RNA Polymerase of Potato virus Y Allows the Simultaneous Breakdown of Two Different Forms of Antiviral Resistance in Capsicum annuum.

The dominant Pvr4 gene in pepper (Capsicum annuum) confers resistance to members of six potyvirus species, all of which belong to the Potato virus Y (PVY) phylogenetic group. The corresponding avirulence factor in the PVY genome is the NIb cistron (i.e., RNA-dependent RNA polymerase). Here, we describe a new source of potyvirus resistance in the Guatemalan accession C. annuum cv. PM949. PM949 is resistant to members of at least three potyvirus species, a subset of those controlled by Pvr4. The F1 progeny between PM949 and the susceptible cultivar Yolo Wonder was susceptible to PVY, indicating that the resistance is recessive. The segregation ratio between resistant and susceptible plants observed in the F2 progeny matched preferably with resistance being determined by two unlinked recessive genes independently conferring resistance to PVY. Inoculations by grafting resulted in the selection of PVY mutants breaking PM949 resistance and, less efficiently, Pvr4-mediated resistance. The codon substitution E472K in the NIb cistron of PVY, which was shown previously to be sufficient to break Pvr4 resistance, was also sufficient to break PM949 resistance, a rare example of cross-pathogenicity effect. In contrast, the other selected NIb mutants showed specific infectivity in PM949 or Pvr4 plants. Comparison of Pvr4 and PM949 resistance, which share the same target in PVY, provides interesting insights into the determinants of resistance durability.

Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity.

This study aims to evaluate the antiviral potential of the nucleoside analogue favipiravir (FAV) against ZIKV, an arbovirus for which there are no approved antiviral therapies, in three human-derived cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and exposed to different concentrations of FAV. Viral supernatant was sampled daily, and infectious viral burden was quantified by plaque assay. Changes in ZIKV infectivity were quantified by calculating specific infectivity. FAV-related toxicities were also assessed for each cell line in both infected and uninfected cells. Our results demonstrate that FAV activity was most pronounced in HeLa cells, as substantial declines in infectious titers and viral infectivity were observed in this cell type. The decline in infectious virus occurred in an exposure-dependent manner and was more pronounced as FAV exposure times increased. Additionally, toxicity studies showed that FAV was not toxic to any of the three cell lines and, surprisingly, caused substantial improvements in the viability of infected HeLa cells. Although SK-N-MC and HUH-7 cells were susceptible to FAV's anti-ZIKV activity, similar effects on viral infectivity and improvements in cell viability with therapy were not observed. These results indicate that FAV's ability to substantially alter viral infectivity is host cell specific and suggest that the robust antiviral effect observed in HeLa cells is mediated through drug-induced losses of viral infectivity.

Understanding routine (non-outbreak) respiratory protective equipment behaviour of hospital workers in different clinical settings – lessons for the future post-COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has drawn attention to the importance of facial (respiratory and eye) protective equipment (FPE). Optimal use of FPE in non-outbreak situations will enable front-line staff, such as emergency department (ED) clinicians, to adapt more rapidly and safely to the increased demands and skills required during an infectious disease outbreak. A survey, designed to determine the attitudes, beliefs and knowledge of healthcare workers around the use of FPE for protection against respiratory infections, was distributed to staff in a respiratory ward, an adult ED and a paediatric ED in Sydney, Australia prior to COVID-19. The survey revealed differences between the respiratory ward and the EDs, and between professional groups. ED staff, particularly paediatric clinicians, were less likely than ward staff to use FPE appropriately during routine care. Medical staff were more likely to work outside of infection prevention and control policies. The busy, relatively chaotic ED environment presents unique challenges for optimal compliance with safe use of FPE when caring for patients with respiratory symptoms. Building upon the lessons of the pandemic, it is timely to address the specific infection prevention and control needs of the ED environment to improve compliance with the use of FPE during non-outbreak situations.

Human brain microphysiological systems in the study of neuroinfectious disorders

Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques, including co-culturing of various cell types, utilization of scaffolds and extracellular matrix materials, perfusion systems, 3D culture methods, 3D bioprinting, organ-on-a-chip technology, and examination of tissue structures. Several human brain 3D cultures or brain MPS (BMPS) have emerged in the last decade. These organoids or spheroids are 3D culture systems derived from induced pluripotent cells or embryonic stem cells that contain neuronal and glial populations and recapitulate structural and physiological aspects of the human brain. BMPS have been introduced recently in the study and modeling of neuroinfectious diseases and have proven to be useful in establishing neurotropism of viral infections, cell-pathogen interactions needed for infection, assessing cytopathological effects, genomic and proteomic profiles, and screening therapeutic compounds. Here we review the different methodologies of organoids used in neuroinfectious diseases including spheroids, guided and unguided protocols as well as microglia and blood-brain barrier containing models, their specific applications, and limitations. The review provides an overview of the models existing for specific infections including Zika, Dengue, JC virus, Japanese encephalitis, measles, herpes, SARS-CoV2, and influenza viruses among others, and provide useful concepts in the modeling of disease and antiviral agent screening.

Financial crises and financial contagion in Japan

The article analyzes the features of the financial crises in Japan in the context of using theoretical and practical approaches to financial contagion. A brief overview of the three significant financial crises observed in the period 1990–2009 is made with the identification of their causes, nature, and consequences. A strong impact on the Japanese economy was exerted by the banking crisis of 1997–2001, which became one of the most noticeable events of the “lost decade”. Its lessons allowed the Japanese government to overcome with minimal losses the global financial crisis of 2007–2009, which negatively affected not so much the credit and stock markets as the real sector of the Japanese economy and its foreign trade.It is productive to consider the spread of crises from the standpoint of the theory and methodology of financial contagion. It is a process of transmission of negative shocks that can lead to the disruption of fundamental links between countries and markets, thereby contributing to the growth of crises and instability. The article shows that Japan can act as both a transmitter and a recipient of infection. Examples of studies that examine the channels and direction of financial contagion in Japan are given. Its important feature is that the main channel for the transmission of shocks in a given country are trade relations, and not the financial ones. Taking this circumstance into account explains the effectiveness of the policy of supporting the real sector of the economy pursued by the Japanese government during the global financial crisis of 2007–2009.In order to illustrate the methodology of financial contagion, the article conducted an empirical study of the country and cross-industry effects of infection in the Japanese economy during the COVID-19 period. A specific infection detection tool (statistical tests) and an extensive empirical database were used. As a result, the country effects were confirmed only partially – Japan was the recipient of the financial contagion that came from China, but only weakly transferred it to other countries. Cross-industry infection spread more actively (it was recorded by more than a half of the tests). At the same time, uneven transmission of shocks between sectors was detected; possible causes of high or low susceptibility to infection in different sectors were discussed.

Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases.

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from -81.304 to -1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (-1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [-873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.

Detection and prevalence of extended spectrum β-lactamases production among Enterobacteriaceae isolated from urinary tract infections

Urinary tract infections (UTIs) by extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) have become an important public health problem with a substantial economic burden, as they lead to more complicated infections, longer duration of treatment, and increases in patient mortality. A total of 1267 urine samples were collected from patients during the period of 2018 to 2020. The isolates were identified based on colony morphology and biochemical tests. Antimicrobial susceptibility testing was done by modified Kirby Bauer disc diffusion method. Resistant isolates to third generation cephalosporins were tested for ESBL production by double-disk synergy test (DDST), DDST methods on MH agar plates supplemented with cloxacillin and by confirmatory double disk test (DDT). 400 strains causing UTIs were identified and classified as members of Enterobacteriaceae. The results of antimicrobial susceptibility tests showed that 68.5% (274/400) of the Enterobacteriaceae isolates were multi-drug resistant (MDR) strains. The overall prevalence of ESBL-E was 59.5% (238/400). The highest frequencies of ESBL-E were observed in internal medicine devices (68/400) and the highest ESBL production was observed in E. coli (85/238). The ESBL producing isolates were significantly resistant to penicillins and cephalosporins compared to non-ESBL producers. However, those ESBL-E strains were sensitive to imipenem (80.2%) and nitrofurantoin (87.8%). High levels of MDR strains and ESBL-E in our study highlights the need for applying specific infection control measures, and accordingly we urge physicians to opt for specific strategies for regular surveillance of uropathogenic bacteria.

Dynamics of an age-structured HIV model with general nonlinear infection rate

Abstract In this paper, the asymptotical behaviour of an age-structured Human Immunodeficiency Virus infection model with general non-linear infection function and logistic proliferation term is studied. Based on the existence of the equilibria and theory of operator semigroups, linearized stability/instability of the disease-free and endemic equilibria is investigated through the distribution of eigenvalues of the linear operator. Then persistence of the solution semi-flow of the considered system is studied by showing the existence of a global attractor and the obtained result shows that the solution semi-flow is persistent as long as the basic reproduction number $R_{0}&amp;gt;1$. Moreover, the Hopf bifurcations problem around the endemic equilibrium is also considered for the situation with a specific infection function. Since the system has two different delays, four cases are discussed to investigate the influence of the time delays on the dynamics of system around the endemic equilibrium including stability and Hopf bifurcations. At last, some numerical examples with concrete parameters are provided to illustrate the obtained results.

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles - Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine.

Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC50=29.5 μg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

8.Prevalence of Transmissible Infections Among Breast Cancer Patients in Calabar, Nigeria

Introduction: Transmissible infections including those of human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis remain public health challenges. The co-existence of these infections with other disease conditions of medical importance can be quite challenging, particularly if there is no prior knowledge of the infection status. Apart from the direct impact on the affected patient, there is also the concern of safety for care givers as well as the risk of nosocomial transmission to other patients. This study focused on pre-operative screening of breast cancer patients to determine the prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis infections. Materials and Methods: This study was conducted among breast cancer patients in Calabar, Cross River State of Nigeria. A structured questionnaire was administered by two trained interviewers to obtain biodata and socio-demographic characteristics. Screening for antibodies to HIV, HBV, HCV and Syphilis were performed by standard serological techniques. Results: General prevalence for all the screened infections was 18%. Distribution of specific infections revealed hepatitis B viral infection to be highest (8%), followed by HIV infection (6%). Hepatitis C virus infection and syphilis were the least with 2% rates each. Among participants living with these infections, 33% had previous knowledge of their status, while the remaining 67% had no prior knowledge. Conclusion: Hepatitis B virus had the highest prevalence while the lowest were HCV and syphilis. Greater percentage of infected subjects were not aware of their status prior to the pre-operative screening.

Genetically engineered pair of cells for serological testing and its application for SARS-CoV-2.

We have developed a serology test platform for identifying individuals with prior exposure to specific viral infections and provide data to help reduce public health risks. The serology testcomposed of a pair of cell lines engineered to express either a viral envelop protein (Target Cell) or a receptor to recognize the Fc region of an antibody (Reporter Cell), that is, Diagnostic-Cell-Complex (DxCell-Complex). The formation of an immune synapse, facilitated by the analyte antibody, resulted into a dual-reporter protein expression by the Reporter Cell. We validated it with human serum with confirmed history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No signal amplification steps were necessary. The DxCell-Complex quantitatively detected the target-specific immunoglobulin G (IgG) within 1h. Validation with clinical human serum containing SARS-CoV-2 IgG antibodies confirmed 97.04% sensitivity and 93.33% specificity. The platform can be redirected against other antibodies. Self-replication and activation-induced cell signaling, two attributes of the cell, will enable rapid and cost-effective manufacturing and its operation in healthcare facilities without requiring time-consuming signal amplification steps.

Differences in characteristics and infection severity between odontogenic and other bacterial oro-naso-pharyngeal infections

BackgroundDifferent bacterial infections of the oro-naso-pharyngeal (ONP) region may progress and require hospital care. The present study clarified differences in infection characteristics between hospitalized patients with odontogenic infections (OIs) and other bacterial ONP infections. The specific aim was to evaluate clinical infection variables and infection severity according to infection aetiology, particularly regarding features of OIs compared with other ONPs.MethodsRecords of patients aged ≥16 years requiring hospital care for an acute bacterial ONP infection in the emergency units of Otorhinolaryngology or Oral and Maxillofacial Surgery at the Helsinki University Hospital (Helsinki, Finland) during 2019 were evaluated retrospectively. The main outcome variables were need for intensive care unit (ICU) treatment and length of hospital stay. The primary predictor variable was infection category, defined as OI or other ONP. The secondary predictor variable was specific ONP infection group. Additional predictor variables were primary clinical infection signs, infection parameters at hospital admission, and delay from beginning of symptoms to hospitalization. Explanatory variables were sex, age, current smoking, heavy alcohol use or substance abuse, and immunosuppressive disease, immunosuppressive medication, or both. Comparison of study groups was performed using Fisher’s exact test, student’s t-test, and Mann-Whitney U.ResultsA total of 415 patients with bacterial ONPs fulfilled the inclusion criteria. The most common infections were oropharyngeal (including peritonsillar, tonsillar, and parapharyngeal infections; 51%) followed by infections from the odontogenic origin (24%). Clinical features of OIs differed from other ONPs. Restricted mouth opening, skin redness, or facial or neck swelling (or both) were found significantly more often in OIs (p < 0.001). OIs required ICU care significantly more often than other ONPs (p < 0.001) and their hospital stay was longer (p = 0.017).ConclusionsInfections originating from the tonsillary and dental origin had the greatest need for hospitalization. Clinical features of OIs differed; the need for ICU treatment was more common and hospital stay was longer compared with other ONPs. Preventive care should be emphasized regarding OIs, and typical infection characteristics of ONP infection subgroups should be highlighted to achieve early and prompt diagnosis and treatment and to reduce hospitalization time.

In-Flight Infection Prevention and Control Training for Cabin Crew in China: A Qualitative Study

Specific in-flight infection prevention and control (IPC) training was deemed an essential strategy for ensuring the implementation of appropriate measures to protect the health of passengers and crew sustainably during COVID-19 and the post-pandemic period. This study aims to identify cabin crew’s IPC duties and investigate the current status of the in-flight IPC training for cabin crew in China. The snowballing technique was employed with purposeful sampling. A total of 15 participants, including cabin crew of various positions, inspectors, and trainers from eight airlines in China were invited to attend the in-depth semi-structured interview between September and November of 2022. Cabin crew IPC duties can be classified into four phases based on a thematic analysis: before flight, passenger boarding, during flight, and after flight. The findings indicated airlines in China required their cabin crew to carry out strict IPC measures onboard throughout all stages of flight, including in-flight IPC training before flight, being aware of COVID symptoms and monitoring passengers’ conditions during boarding, the standard operating procedure (SOP) of handling suspicious carriers during flight, and so on. Meanwhile, six major themes concerning cabin crew’s in-flight IPC training were extracted: COVID-19 information, IPC Supplies and usage, IPC measures onboard, communication and explanation, information collection and report up, attitude and perceptions toward COVID-19, and IPC measures. Cabin crew were regularly trained on in-flight IPC through online learning, with face-to-face training used as reinforcement. Although training for knowledge and technical skills was deemed comprehensive, non-technical skills such as communication and explanation were viewed as a weak link. Moreover, airlines should make greater efforts to help cabin crew develop a positive attitude towards COVID-19 and overcome their internal fears. This study pointed out the shortcomings of the in-flight IPC training for cabin crew in China and can help the airlines improve the training program so that cabin crew can perform their duties correctly. Furthermore, the result can inform the development of future cabin crew training programs for the post-pandemic period.